11-67417581-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020811.2(CARNS1):c.-192C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000812 in 1,355,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CARNS1
NM_020811.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

Publications

0 publications found

Variant links:

Genes affected

CARNS1 (HGNC:29268): (carnosine synthase 1) CARNS1 (EC 6.3.2.11), a member of the ATP-grasp family of ATPases, catalyzes the formation of carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-aminobutyryl-L-histidine), which are found mainly in skeletal muscle and the central nervous system, respectively (Drozak et al., 2010 [PubMed 20097752]).[supplied by OMIM, Apr 2010]

CARNS1 links:

PPP1CA (HGNC:9281): (protein phosphatase 1 catalytic subunit alpha) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). This broadly expressed gene encodes the alpha subunit of the PP1 complex that associates with over 200 regulatory proteins to form holoenzymes which dephosphorylate their biological targets with high specificity. PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity has been observed in the end stage of heart failure. Studies suggest that PP1 is an important regulator of cardiac function and that PP1 deregulation is implicated in diabetes and multiple types of cancer. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2020]

PPP1CA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2476916).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020811.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CARNS1	NM_001166222.2	MANE Select	c.178C>T	p.Arg60Trp	missense	Exon 3 of 10	NP_001159694.1	A5YM72-5
CARNS1	NM_020811.2		c.-192C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_065862.1	A5YM72-1
CARNS1	NM_001394577.1		c.178C>T	p.Arg60Trp	missense	Exon 3 of 9	NP_001381506.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CARNS1	ENST00000307823.7	TSL:1	c.-192C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	ENSP00000308268.3	A5YM72-1
CARNS1	ENST00000687366.1	MANE Select	c.178C>T	p.Arg60Trp	missense	Exon 3 of 10	ENSP00000510668.1	A5YM72-5
CARNS1	ENST00000307823.7	TSL:1	c.-192C>T		5_prime_UTR	Exon 2 of 9	ENSP00000308268.3	A5YM72-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000748

AC:

AN:

1203032

Hom.:

Cov.:

AF XY:

0.0000103

AC XY:

AN XY:

582140

show subpopulations

African (AFR)

AF:

0.0000408

AC:

AN:

24488

American (AMR)

AF:

0.00

AC:

AN:

12386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17384

East Asian (EAS)

AF:

0.00

AC:

AN:

27954

South Asian (SAS)

AF:

0.00

AC:

AN:

51690

European-Finnish (FIN)

AF:

0.0000348

AC:

AN:

28720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4988

European-Non Finnish (NFE)

AF:

0.00000710

AC:

AN:

986054

Other (OTH)

AF:

0.00

AC:

AN:

49368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Benign

0.099

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.88

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

PhyloP100

2.7

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.093

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.010

Vest4

0.29

MVP

0.49

MPC

0.35

ClinPred

0.96

GERP RS

2.6

gMVP

0.31

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over